THERMODYNAMICS OF AMINO-ACID SIDE-CHAIN INTERNAL ROTATIONS

The absolute Gibbs energy, enthalpy and entropy of each of the interna l rotations found in protein side chains has been calculated. The calc ulation requires the moments of inertia of the side chains about each bond, the potential energy barrier and the symmetry number and gives t he maximum possible thermodynamic consequences of restricting side cha in motion when a protein folds. Hindering side chain internal rotation s is unfavourable in terms of Gibbs energy and entropy; it is enthalpi cally favourable at 0K. At room temperature, it is estimated that the adverse entropy of hindering buried side chain internal rotation is on ly 25% of the absolute entropy. The difference between absolute entrop ies in the folded and unfolded states gives the entropy change for fol ding. The estimated Gibbs energy change for restricting each residue c orrelates moderately well with the probability of that residue being f ound on the folded protein surface, rather than in the protein interio r (where motion is restricted).